Processing of the beta-amyloid precursor protein (APP) leads to a range of proteolyzed forms (1-6), some of which assemble into beta-amyloid fibrils and are cytotoxic. .beta.-amyloid moieties, such as amyloid-beta peptide (A.beta.), are closely associated with neuronal dysfunction and death in Alzheimer's disease (AD). Increased expression of amyloid-beta peptide is linked to mutations in APP (6-10) and in presenilins (11-13), both of which occur in familial AD. The mechanisms underlying the cellular stress phenotype brought about in cells by amyloid-beta peptide-derived peptides are likely related to the neurotoxicity leading to dementia. Most attention has been focussed on mechanisms by which extracellular amyloid-beta peptide exerts its effects on cells, since the most visible accumulations of amyloid-beta peptide occur extracellularly in plaques. Amyloid-beta peptide aggregates, especially those that assemble into fibrils, can be cytotoxic by nonspecifically disturbing the integrity of cell membranes, and by elaborating reactive oxygen intermediates (14-15), thereby resulting in elevation of cytosolic calcium eventually followed by cell death (15-16). Cell surface receptors for amyloid-beta peptide (17-19) could also activate signal transduction mechanisms. The receptor RAGE, an immunoglobulin superfamily molecule, is one such neuronal cell surface docking site which binds amyloid-beta peptide and facilitates amyloid-beta peptide-mediated cellular oxidant stress (19).